There are two main objectives in this research: 1) A study of the mechanisms by which resistance transfer factors (R-factors) determine antibiotic resistance in clinical isolates of bacteria and the nature of the regulation of synthesis of R-factor coded products. The work will concentrate on the aminoglycoside antibiotics in clinical use. 2) The application of antibiotics and mutations to antibiotic resistance to a study of ribosome structure and function in Escherichia coli. This will include the characterization of new ribosomal protein genes and the role of ribosomal proteins in various aspects of ribosome function and biosynthesis. As an adjunct to this, the mode of action of antibiotics interfering rith ribosomal function will be examined.